Over-expression of FOXM1 is associated with cell migration/invasion of ovarian cancer cells

Abstract

FOXM1 is a typical transcription factor regulating the S- and M-phase progression in cell cycle. It is frequently over-expressed and is associated with tumor stages in numerous human cancers. The influence of FOXM1 expression on cell proliferation has been well studied, yet its impact on other tumor characteristics in ovarian cancer, like cell migration/invasion remains unclear. In the present study, we demonstrated that FOXM1 was significantly up-regulated in ovarian cancer cell lines at both RNA and protein level by semi-quantitative RT- PCR and Western blot analyses. Immunohistochemical analysis showed that FOXM1 was highly correlated with the high-grade ovarian cancer. To examine the effect of FOXM1 on ovarian cancer cell motility, the FOXM1 specific inhibitor, thiostrepton, was used to reduce FOXM1 expression in OVCA433 cells. The FOXM1 reduced OVCA433 cells, as a result, showed a significant decrease in cell migration using wound healing assay. By using MEK specific inhibitor, U0126, we demonstrated that the inhibition of ERK activity caused a reduction of FOXM1 level in a time dependent manner and significant reduction of cell migration rate in the wound healing assay in OVCA433. In sum, FOXM1 is over-expressed and regulated by constitutive activated ERK activity in ovarian cancer cells. Our data also suggested that the ERK /FOXM1 signaling axis is crucial in regulating migration/invasion of ovarian cancer cells. Further studies on the molecular mechanism of FOXM1 in the regulation of ovarian cancer cell migration/invasion are warranted.